Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).

Expansion of Telestroke Coverage in Community Hospitals: Unifying Stroke Care and Reducing Transfer Rate.

OBJECTIVE: Telestroke (TS) service has been shown to improve stroke diagnosis timing and accuracy, facilitate treatment decisions, and decrease interfacility transfers. Expanding TS service to inpatient units at the community hospital provides an opportunity to follow up on stroke patients and optimize medical management. This study examines the outcome of expanding TS coverage from acute emergency room triage to incorporate inpatient consultation. METHODS: We studied the effect of expanding TS to inpatient consultation service at 19 regional hospitals affiliated with Promedica Stroke Network. We analyzed data pre- and post-TS expansion. We reviewed changes in TS utilization, admission rate, thrombolytic therapy, patient transfer rate, and diagnosis accuracy. RESULTS: Between January 2018 and June 2022, a total of 9,756 patients were evaluated in our stroke network (4,705 in pre- and 5,051 in the post-TS expansion). In the post-TS expansion period, stroke patients' admission at the spoke hospital increased from 18/month to 40/month, and for TIA from 11/month to 16/month. TS cart use increased from 12% to 35.2%. Patient transfers to hub hospital decreased by 31%. TS service expansion did not affect intravenous thrombolytic therapy rate or door-to-needle time. There was no difference in length of stay or readmission rate, and the patients at the spoke hospitals had a higher rate of home discharge 57.38% compared with 52.58% at hub hospital. INTERPRETATION: Telestroke service expansion to inpatient units helped decrease transfers and retain patients in their communities, increased stroke and TIA diagnosis accuracy, and did not compromise patients' hospitalization or outcome. ANN NEUROL 2024;95:576-582.

Cervical Dissection in Patients With Tandem Lesions Is Associated With Distal Embolism and Lower Recanalization Success.

BACKGROUND: Tandem lesions consist of cervical internal carotid artery (ICA) stenosis or occlusion, most commonly of atherosclerosis or dissection etiology, plus a large vessel occlusion. In this study, we compare outcomes in patients with atherosclerosis versus dissection of the cervical ICA. METHODS: This multicenter retrospective cohort study includes data from tandem lesion patients who underwent endovascular treatment from 2015 to 2020. Atherosclerosis was defined as ICA stenosis/occlusion associated with a calcified lesion and dissection by the presence of a tapered or flame-shaped lesion and intramural hematoma. Primary outcome: 90-day functional independence (modified Rankin Scale score, 0-2); secondary outcomes: 90-day favorable shift in the modified Rankin Scale score, modified Thrombolysis in Cerebral Infarction score 2b-3, modified Thrombolysis in Cerebral Infarction score 2c-3, symptomatic intracranial hemorrhage, parenchymal hematoma type 2, petechial hemorrhage, distal embolization, early neurological improvement, and mortality. Analysis was performed with matching by inverse probability of treatment weighting. RESULTS: We included 526 patients (68 [59-76] years; 31% females); 11.2% presented dissection and 88.8%, atherosclerosis. Patients with dissection were younger, had lower rates of hypertension, hyperlipidemia, diabetes, and smoking history. They also exhibited higher rates of ICA occlusion, multiple stents (>1), and lower rates of carotid self-expanding stents. After matching and adjusting for covariates, there were no differences in 90-day functional independence. The rate of successful recanalization was significantly lower in the dissection group (adjusted odds ratio, 0.38 [95% CI, 0.16-0.91]; P=0.031), which also had significantly higher rates of distal emboli (adjusted odds ratio, 2.53 [95% CI, 1.15-5.55]; P=0.021). There were no differences in other outcomes. Acute ICA stenting seemed to increase the effect of atherosclerosis in successful recanalization. CONCLUSIONS: This study reveals that among patients with acute stroke with tandem lesions, cervical ICA dissection is associated with higher rates of distal embolism and lower rates of successful recanalization than atherosclerotic lesions. Using techniques to minimize the risk of distal embolism may mitigate this contrast. Further prospective randomized trials are warranted to fully understand these associations.

Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke.

BACKGROUND: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well. METHODS: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT. RESULTS: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P<0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P=0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P=0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P=0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P=0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well. CONCLUSIONS: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

Sex Differences in Outcomes of Late-Window Endovascular Stroke Therapy.

BACKGROUND: The association between sex and outcome after endovascular thrombectomy of acute ischemic stroke is unclear. The aim of this study was to compare the clinical and safety outcomes between men and women treated with endovascular thrombectomy in the late 6-to-24-hour window period. METHODS: This multicenter, retrospective observational cohort study included consecutive patients who underwent endovascular thrombectomy of anterior circulation stroke in the late window from 66 clinical sites in 10 countries from January 2014 to May 2022. The primary outcome was the 90-day ordinal modified Rankin Scale score. Secondary outcomes included 90-day functional independence (FI), return of Rankin (RoR) to prestroke baseline, FI or RoR, symptomatic intracranial hemorrhage, and mortality. Multivariable and inverse probability of treatment weighting methods were used. We explored the interaction of sex with baseline characteristics on the outcomes ordinal modified Rankin Scale and FI or RoR. RESULTS: Of 1932 patients, 1055 were women and 877 were men. Women were older (77 versus 69 years), had higher rates of atrial fibrillation, hypertension, and greater prestroke disability, but there was no difference in baseline National Institutes of Health Stroke Scale score. Inverse probability of treatment weighting analysis showed no difference between women and men in ordinal modified Rankin Scale (odds ratio, 0.98 [95% CI, 0.79-1.21]), FI or RoR (odds ratio, 0.98 [95% CI, 0.78-1.22]), severe disability or mortality (odds ratio, 0.99 [95% CI, 0.80-1.23]). The multivariable analysis of the above end points was concordant. There were no interactions between baseline characteristics and sex on the outcomes of ordinal modified Rankin Scale and FI or RoR. CONCLUSIONS: In late presenting patients with anterior circulation stroke treated with endovascular thrombectomy in the 6 to 24-hour window, there was no difference in clinical or safety outcomes between men and women.

Itaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection.

Excessive inflammation is a major cause of morbidity and mortality in many viral infections including influenza. Therefore, there is a need for therapeutic interventions that dampen and redirect inflammatory responses and, ideally, exert antiviral effects. Itaconate is an immunomodulatory metabolite which also reprograms cell metabolism and inflammatory responses when applied exogenously. We evaluated effects of endogenous itaconate and exogenous application of itaconate and its variants dimethyl- and 4-octyl-itaconate (DI, 4OI) on host responses to influenza A virus (IAV). Infection induced expression of ACOD1, the enzyme catalyzing itaconate synthesis, in monocytes and macrophages, which correlated with viral replication and was abrogated by DI and 4OI treatment. In IAV-infected mice, pulmonary inflammation and weight loss were greater in Acod1-/- than in wild-type mice, and DI treatment reduced pulmonary inflammation and mortality. The compounds reversed infection-triggered interferon responses and modulated inflammation in human cells supporting non-productive and productive infection, in peripheral blood mononuclear cells, and in human lung tissue. All three itaconates reduced ROS levels and STAT1 phosphorylation, whereas AKT phosphorylation was reduced by 4OI and DI but increased by itaconate. Single-cell RNA sequencing identified monocytes as the main target of infection and the exclusive source of ACOD1 mRNA in peripheral blood. DI treatment silenced IFN-responses predominantly in monocytes, but also in lymphocytes and natural killer cells. Ectopic synthesis of itaconate in A549 cells, which do not physiologically express ACOD1, reduced infection-driven inflammation, and DI reduced IAV- and IFNγ-induced CXCL10 expression in murine macrophages independent of the presence of endogenous ACOD1. The compounds differed greatly in their effects on cellular gene homeostasis and released cytokines/chemokines, but all three markedly reduced release of the pro-inflammatory chemokines CXCL10 (IP-10) and CCL2 (MCP-1). Viral replication did not increase under treatment despite the dramatically repressed IFN responses. In fact, 4OI strongly inhibited viral transcription in peripheral blood mononuclear cells, and the compounds reduced viral titers (4OI>Ita>DI) in A549 cells whereas viral transcription was unaffected. Taken together, these results reveal itaconates as immunomodulatory and antiviral interventions for influenza virus infection.

Correction: Itaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection.

[This corrects the article DOI: 10.1371/journal.ppat.1010219.].

Predicting Functional Outcome Using 24-Hour Post-Treatment Characteristics: Application of Machine Learning Algorithms in the STRATIS Registry.

FOR SOCIAL MEDIA: @AliciaCastongu2, @FazalZaidi9, @oozaidat, @Mouhammad_Jumaa OBJECTIVE: Machine learning (ML) algorithms have emerged as powerful predictive tools in the field stroke. Here, we examine the predictive accuracy of ML models for predicting functional outcomes using 24-hour post-treatment characteristics in the Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke (STRATIS) Registry. METHODS: ML models, adaptive boost, random forest (RF), classification and regression trees (CART), C5.0 decision tree (C5.0), support vector machine (SVM), least absolute shrinkage and selection operator (LASSO), and logistic regression (LR), and traditional LR models were used to predict 90-day functional outcome (modified Rankin Scale score 0-2). Twenty-four-hour National Institutes of Health Stroke Scale (NIHSS) was examined as a continuous or dichotomous variable in all models. Model accuracy was assessed using the area under characteristic curve (AUC). RESULTS: The 24-hour NIHSS score was a top-predictor of functional outcome in all models. ML models using the continuous 24-hour NIHSS scored showed moderate-to-good predictive performance (range mean AUC: 0.76-0.92); however, RF (AUC: 0.92 ± 0.028) outperformed all ML models, except LASSO (AUC: 0.89 ± 0.023, p = 0.0958). Importantly, RF demonstrated a significantly higher predictive value than LR (AUC: 0.87 ± 0.031, p = 0.048) and traditional LR (AUC: 85 ± 0.06, p = 0.035) when using the 24-hour continuous NIHSS score. Predictive accuracy was similar between the 24-hour NIHSS score dichotomous and continuous ML models. INTERPRETATION: In this substudy, we found similar predictive accuracy for functional outcome when using the 24-hour NIHSS score as a continuous or dichotomous variable in ML models. ML models had moderate-to-good predictive accuracy, with RF outperforming LR models. External validation of these ML models is warranted. ANN NEUROL 2023;93:40-49.

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are essentially different manifestations of the same disease that are similarly managed. A number of molecular and cytogenetic variables with prognostic implications have been identified. Undetectable minimal residual disease at the end of treatment with chemoimmunotherapy or venetoclax-based combination regimens is an independent predictor of improved survival among patients with previously untreated or relapsed/refractory CLL/SLL. The selection of treatment is based on the disease stage, presence or absence of del(17p) or TP53 mutation, immunoglobulin heavy chain variable region mutation status, patient age, performance status, comorbid conditions, and the agent's toxicity profile. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with CLL/SLL.

Early Versus Late Feeding After Percutaneous Endoscopic Gastrostomy Placement in Trauma and Burn.

INTRODUCTION: Timing to resume feeds after percutaneous endoscopic gastrostomy (PEG) placement continues to vary among US trauma surgeons. The purpose of this study was to assess differences in meeting nutritional therapy goals and adverse outcomes with early versus late enteral feeding after PEG placement. METHODS: This retrospective review included 364 trauma and burn patients who underwent PEG placement. Data included patient characteristics, time to initiate feeds, rate feeds were resumed, % feed volume goals on postoperative days 0-7, and complications. Statistical analysis was performed comparing two groups (feeds ≤ 6 h versus > 6 h) and three subgroups (< 4 h, 4-6 h, ≥ 6 h) based on data quartiles. Chi-square/Fisher's exact test, independent-samples t-test, and one-way analysis of variance were used to analyze the data. RESULTS: Mean time to initiate feeds after PEG was 5.48 ± 4.79 h. Burn patients received early feeds in a larger proportion. A larger proportion of trauma patients received late feeds. The mean % of goal feed volume met on postoperative day 0 was higher in the early feeding group versus the late (P < 0.001). There were no differences in adverse events, even after subgroup analysis of those who received feeds < 4 h after PEG placement. CONCLUSIONS: Patients with early initiation of feeds after PEG placement achieve a higher percentage of goals on day 0 without an increased rate of adverse events. Unfortunately, patients routinely fall short of their target tube feeding goals.

The risk analysis index demonstrates exceptional discrimination in predicting frailty's impact on neurosurgical length of stay quality metrics.

BACKGROUND: Quality measures determine reimbursement rates and penalties in value-based payment models. Frailty impacts these quality metrics across surgical specialties. We compared the discriminatory thresholds for the risk analysis index (RAI), modified frailty index-5 (mFI-5) and increasing patient age for the outcomes of extended length of stay (LOS [eLOS]), prolonged LOS within 30 days (pLOS), and protracted LOS (LOS > 30). METHODS: Patients ≥18 years old who underwent neurosurgical procedures between 2012 and 2020 were queried from the ACS-NSQIP. We performed receiver operating characteristic analysis, and multivariable analyses to examine discriminatory thresholds and identify independent associations. RESULTS: There were 411,605 patients included, with a median age of 59 years (IQR, 48-69), 52.2% male patients, and a white majority 75.2%. For eLOS: RAI C-statistic 0.653 (95% CI: 0.652-0.655), versus mFI-5 C-statistic 0.552 (95% CI: 0.550-0.554) and increasing patient age C-statistic 0.573 (95% CI: 0.571-0.575). Similar trends were observed for pLOS- RAI: 0.718, mFI-5: 0.568, increasing patient age: 0.559, and for LOS>30- RAI: 0.714, mFI-5: 0.548, and increasing patient age: 0.506. Patients with major complications had eLOS 10.1%, pLOS 26.5%, and LOS >30 45.5%. RAI showed a larger effect for all three outcomes, and major complications in multivariable analyses. CONCLUSION: Increasing frailty was associated with three key quality metrics that is, eLOS, pLOS, LOS > 30 after neurosurgical procedures. The RAI demonstrated a higher discriminating threshold compared to both mFI-5 and increasing patient age. Preoperative frailty screening may improve quality metrics through risk mitigation strategies and better preoperative communication with patients and their families.

The Impact of Hidradenitis Suppurativa on Work Productivity and Performance: a Systematic Review and Meta-Analysis.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder affecting the skinfold regions. There is growing appreciation of the need for socioeconomic factors to be included in multidisciplinary assessments of HS. However, knowledge regarding HS and workplace function is limited. OBJECTIVES: To assess the relationship between HS and workplace function. METHODS: Cinahl, Embase, MedLine, PsycInfo and PubMed were systematically searched to collect data from studies in which validated surveys of workplace function were administered to HS patients. RESULTS: Out of 1,932 publications, twelve studies were included in this review and seven reported sufficient data for meta-analysis. Included studies encompassed 5,187 HS patients and no controls. All studies employed the Work Productivity and Activity Impairment questionnaire, reporting percentage scores for absenteeism, presenteeism, total work productivity impairment (TWPI) and total activity impairment (TAI). Pooled mean scores for HS were calculated as 10.17% (95%CI 8.68-11.66) for absenteeism, 31.13% (95%CI 25.02-37.23) for presenteeism, 34.25% (95%CI 29.37-39.14) for TWPI, and 42.23% (95%CI 38.56-45.89) for TAI. Significant heterogeneity was identified and most studies were of 'poor' to 'fair' quality. CONCLUSIONS: Current evidence suggests considerable impairment of workplace functioning in HS patients. Our findings point to a significant unmet treatment need with respect to improving working capability in HS. The extant literature is inadequate to reliably assess the mechanisms underlying this effect or to comparatively assess the capabilities of HS therapies to improve workplace function.

Systolic blood pressure reduction strategies in acute ischemic stroke patients following endovascular thrombectomy: a systematic review and meta-analysis.

BACKGROUND AND AIMS: There is no clear consensus on ideal systolic blood pressure (SBP) target post-endovascular thrombectomy (EVT) in patients with acute ischemic stroke. This study intends to investigate the relationship between reducing SBP and clinical outcomes and to determine the therapeutic efficacy of moderate and intensive SBP reduction post EVT. METHODS: A comprehensive search was conducted across five electronic databases to identify studies relevant to our analysis. Data from these studies were then analyzed using pooled relative risk (RR) along with their corresponding 95 % confidence intervals (CI) for our categorical outcomes. functional independence at 90 days post-EVT was defined as a modified Rankin score (mRS) 0-2. RESULTS: Our meta-analysis included eight studies with 2922 patients: 1376 patients were treated with intensive SBP reduction, 306 with moderate SBP reduction, and 1243 with standard SBP reduction. There was no difference in the risk of functional independence at 90 days post-EVT with both intensive-SBP reduction (target 120-140 mmHg, relative risk (RR) =1.05, 95 % CI 0.82, 1.34, p = 0.72) and moderate-SBP reduction (>160 mm Hg) (RR= 0.95, 95 % CI 0.69, 1.31, p = 0.76) compared with standard SBP reduction (>180 mm Hg). The risk of symptomatic intracranial hemorrhage (sICH) did not significantly differ between standard-SBP reduction and intensive-SBP reduction (RR = 0.93, 95 % CI 0.66, 1.31, p = 0.36) or moderate-SBP reduction (0.72 (95 % CI [0.28, 1.87], p = 0.50) groups, respectively. Intensive-SBP reduction significantly decreased the risk of hemicraniectomy. CONCLUSIONS: We did not identify any difference in functional independence at 90 days in acute ischemic stroke patients with either intensive-SBP reduction or moderate-SBP reduction compared with standard SBP reduction post-EVT.

Effector-triggered inhibition of nodulation: A rhizobial effector protease targets soybean kinase GmPBS1-1.

Type III protein secretion systems of nitrogen-fixing rhizobia deliver effector proteins into leguminous host cells to promote or inhibit the nodule symbiosis. However, mechanisms underlying effector-triggered inhibition of nodulation remain largely unknown. Nodulation outer protein T (NopT) of Sinorhizobium sp. NGR234 is an effector protease related to the Pseudomonas effector Avirulence protein Pseudomonas phaseolicola B (AvrPphB). Here, we constructed NGR234 mutants producing different NopT variants and found that protease activity of NopT negatively affects nodulation of smooth crotalaria (Crotalaria pallida). NopT variants lacking residues required for autocleavage and subsequent lipidation showed reduced symbiotic effects and were not targeted to the plasma membrane. We further noticed that Sinorhizobium fredii strains possess a mutated nopT gene. Sinorhizobium fredii USDA257 expressing nopT of NGR234 induced considerably fewer nodules in soybean (Glycine max) cv. Nenfeng 15 but not in other cultivars. Effector perception was further examined in NopT-expressing leaves of Arabidopsis (Arabidopsis thaliana) and found to be dependent on the protein kinase Arabidopsis AvrPphB Susceptible 1 (AtPBS1) and the associated resistance protein Arabidopsis Resistance to Pseudomonas syringae 5 (AtRPS5). Experiments with Nicotiana benthamiana plants indicated that the soybean homolog GmPBS1-1 associated with AtRPS5 can perceive NopT. Further analysis showed that NopT cleaves AtPBS1 and GmPBS1-1 and thus can activate these target proteins. Insertion of a DKM motif at the cleavage site of GmPBS1-1 resulted in increased proteolysis. Nodulation tests with soybeans expressing an autoactive GmPBS1-1 variant indicated that activation of a GmPBS1-1-mediated resistance pathway impairs nodule formation in cv. Nenfeng 15. Our findings suggest that legumes face an evolutionary dilemma of either developing effector-triggered immunity against pathogenic bacteria or establishing symbiosis with suboptimally adapted rhizobia producing pathogen-like effectors.

Risk factors for percutaneous left ventricular assist device explant complications.

INTRODUCTION: Percutaneous left ventricular assist device (pLVAD) explant remains nonstandardized with potential complications of bleeding and thrombosis. Explant settings include percutaneous techniques in the catheterization laboratory (CL), manually at bedside (MB), and surgically in the operating room (OR). OBJECTIVE: Identify high-risk features for explant-related complications, including indication for support, setting, and technique. METHODS: Postexplant bleeding and thrombosis/limb ischemia were identified following pLVAD removals over 2 years at a multicenter healthcare system. RESULTS: Of 156 patients, bleeding (n = 26 [17%]) and thrombosis (n = 9 [6%]) occurred more often in patients with the peripheral arterial disease (PAD), female gender, anemia, and cardiogenic shock. OR explants had a higher combined endpoint (4/8 [50%]) versus CL (23/133 [17%], p < 0.05) driven by transfusion. There was no difference between OR versus MB (5/15 [33%], p = 0.66) or CL versus MB (p = 0.62). In shock patients, there was no difference between CL (7/30 [23%]) versus MB (5/15 [33%], p = 0.5) and OR (4/7 [57%], p = 0.16); or MB versus OR (p = 0.38). Average length of stay was significantly lower in the CL group versus MB and OR (3.6 ± 33.2 vs. 18.4 ± 10.9 vs. 28.1 ± 15.8 days, p < 0.0001). Preclosure in shock patients (5/25 [20%] vs. 11/27 [41%], p = 0.1383) and crossover balloon occlusion technique (9/44 [16%] vs. 25/112 [22%]; p = 1) were not associated with higher combined endpoints versus control. CONCLUSION: Risk factors for pLVAD explant complications include PAD, female gender, and cardiogenic shock. There was no difference in complication rates between explant settings among cardiogenic shock patients, but shorter length of stay when performed in the CL. There was no difference in complication rates when using the crossover balloon occlusion technique.

Ethics Principles for Artificial Intelligence-Based Telemedicine for Public Health.

The use of artificial intelligence (AI) in the field of telemedicine has grown exponentially over the past decade, along with the adoption of AI-based telemedicine to support public health systems. Although AI-based telemedicine can open up novel opportunities for the delivery of clinical health and care and become a strong aid to public health systems worldwide, it also comes with ethical risks that should be detected, prevented, or mitigated for the responsible use of AI-based telemedicine in and for public health. However, despite the current proliferation of AI ethics frameworks, thus far, none have been developed for the design of AI-based telemedicine, especially for the adoption of AI-based telemedicine in and for public health. We aimed to fill this gap by mapping the most relevant AI ethics principles for AI-based telemedicine for public health and by showing the need to revise them via major ethical themes emerging from bioethics, medical ethics, and public health ethics toward the definition of a unified set of 6 AI ethics principles for the implementation of AI-based telemedicine. (Am J Public Health. 2023;113(5):577-584. https://doi.org/10.2105/AJPH.2023.307225).

The Association of Mental Illness With Outcomes of Emergency Surgery for Bowel Obstruction.

INTRODUCTION: Bowel obstruction is one of the most common surgical emergencies. The management of SBO is variable and influenced by numerous confounding factors. Recent studies have identified mental health as a health disparity that affects surgical outcomes. We aim to assess whether mental illness is a health disparity and its association with postoperative complications and secondary outcomes for bowel obstruction in Emergency General Surgery (EGS). METHODS: This was a retrospective study utilizing the National Inpatient Sample. Individuals aged 18-64 who underwent emergency adehesiolysis or bowel resection from 2015 to 2017 were identified. Postoperative complications, in-hospital mortality, length of stay, and total cost for surgical patients with and without mental illness were recorded. Univariate and multivariate analyses were used to evaluate the association between mental health and bowel obstruction. RESULTS: 20,574 patients who underwent surgery for bowel obstruction were identified. 3756 of these patients had mental illness and 16,998 patients did not. Patients with mental illness did not have significantly worse outcomes compared to patients without mental illness. Among 3576 patients with mental illness, sex, race, patient location, insurance, location/teaching status of hospital, hospital control and procedure type were significant predictors of prolonged length of stay, higher cost, and increased postoperative complications. CONCLUSIONS: Mental health does not appear to be a health disparity in outcomes for bowel obstruction procedures. However, the intersection of mental health with race and insurance status predicts worse outcomes. This essential area should be further explored to determine how marginalized populations are affected in emergency surgical care.

The Mediating Effect of Operative Approach on Racial Disparities in Bariatric Surgery Complications.

INTRODUCTION: A laparoscopic approach to bariatric surgeries confers a favorable side-effect profile as compared to an open approach. However, literature regarding the independent association of race with access to and postoperative outcomes in laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (GS) is scarce. MATERIALS AND METHODS: All RYGB and GS cases recorded in American College of Surgeons National Quality Improvement Program data from 2012 to 2020 were subjected to propensity score matching to assess the independent association between Black self-identified race on access to a laparoscopic approach and postoperative complications. Finally, a series of logistic regressions enabled evaluation of the mediating effect of operative approach on racial disparities in postoperative complications. RESULTS: 55,846 cases of RYGB and 94,209 cases of GS were identified. Following propensity score matching, logistic regression identified Black race as an independent predictor of open approach to RYGB (P < 0.001) and GS (P = 0.019). Black patients had increased incidence of any, minor and severe postoperative complications and unplanned readmissions in both RYGB (P < 0.001, P < 0.001, P = 0.0412, and P < 0.001, respectively) and GS (P < 0.001, P < 0.001, P = 0.0037, and P < 0.001, respectively). Open approach to RYGB was identified as a partial mediator of the independent association between Black race and any complication, minor complications, and unplanned readmission. CONCLUSIONS: This methodology identified racial disparities in complications following RYGB and GS. Interestingly, reduced access to a laparoscopic approach mediated racial disparities in complications following RYGB but not GS. Further research might elucidate upstream determinants of health that catalyze these disparities.

ATM phosphorylates PP2A subunit A resulting in nuclear export and spatiotemporal regulation of the DNA damage response.

Ataxia telangiectasia mutated (ATM) is a serine-threonine protein kinase and important regulator of the DNA damage response (DDR). One critical ATM target is the structural subunit A (PR65-S401) of protein phosphatase 2A (PP2A), known to regulate diverse cellular processes such as mitosis and cell growth as well as dephosphorylating many proteins during the recovery from the DDR. We generated mouse embryonic fibroblasts expressing PR65-WT, -S401A (cannot be phosphorylated), and -S401D (phospho-mimetic) transgenes. Significantly, S401 mutants exhibited extensive chromosomal aberrations, impaired DNA double-strand break (DSB) repair and underwent increased mitotic catastrophe after radiation. Both S401A and the S401D cells showed impaired DSB repair (nonhomologous end joining and homologous recombination repair) and exhibited delayed DNA damage recovery, which was reflected in reduced radiation survival. Furthermore, S401D cells displayed increased ERK and AKT signaling resulting in enhanced growth rate further underscoring the multiple roles ATM-PP2A signaling plays in regulating prosurvival responses. Time-lapse video and cellular localization experiments showed that PR65 was exported to the cytoplasm after radiation by CRM1, a nuclear export protein, in line with the very rapid pleiotropic effects observed. A putative nuclear export sequence (NES) close to S401 was identified and when mutated resulted in aberrant PR65 shuttling. Our study demonstrates that the phosphorylation of a single, critical PR65 amino acid (S401) by ATM fundamentally controls the DDR, and balances DSB repair quality, cell survival and growth by spatiotemporal PR65 nuclear-cytoplasmic shuttling mediated by the nuclear export receptor CRM1.

Intra-arterial thrombolysis as adjunct to mechanical thrombectomy in acute ischemic stroke patients in the United States: A case control analysis.

BACKGROUND: Although observational studies have reported favorable clinical outcomes associated with intra-arterial thrombolysis as adjunct to mechanical thrombectomy, the cost and length of hospitalization associated with this intervention has not been studied. METHODS: We analyzed the nationally representative data of the United States data from Nationwide Inpatient Sample (NIS) to compare hospitalization cost and duration in addition to other outcomes in patients receiving (n = 1990) with those not receiving intra-arterial thrombolysis (n = 1990) in acute ischemic stroke patients undergoing mechanical thrombectomy using a case control design matched for age, gender, and presence of aphasia, hemiplegia, neglect, coma/stupor, hemianopsia and dysphagia. RESULTS: There was no difference in the median hospitalization cost in patients treated with intra-arterial thrombolysis compared with those not treated with intra-arterial thrombolysis: $36,992 [28,361 to 54,336] versus $35,440 [24,383 to 50,438], (regression coefficient 2,485 [-1,947 to 6,917], p = 0.27). There was no difference in the median length of hospitalization in patients treated with intra-arterial thrombolysis compared with those not treated with intra-arterial thrombolysis: 6 days [3 to 10] versus 6 days [4 to 10], (regression coefficient -0.34 [-1.47 to 0.80], p = 0.56). There was no difference in odds of home-discharge (OR 1.02 95%CI 0.72-1.43, p = 0.93) or post-procedural intracranial hemorrhage (OR 1.16 95%CI 0.83-1.64, p = 0.39) between the two groups. CONCLUSIONS: We did not observe an increase in the cost or length of hospitalization associated with the use of intra-arterial thrombolysis as adjunct to mechanical thrombectomy in acute ischemic stroke patients. If the ongoing randomized clinical trials demonstrate therapeutic efficacy in reducing death or disability, this intervention has a high likelihood of being beneficial overall.